Chiral Ligand-Controlled Asymmetric Conjugate Addition of Lithium Amides to Enoates

Abstract

Conjugate addition of nucleophiles to α,β-unsaturated carbonyl compounds is one of the most powerful bond forming reactions and has been widely utilized as a key reaction in organic synthesis. We have been engaged in the chiral ligand-controlled asymmetric reactions of various types of nucleophiles such as organolithiums, organocoppers, organoboranes, and arylthiols. The asymmetric conjugate addition reaction of lithium N-benzyltrimethylsilylamide 2 with tert-butyl enoates 3 bearing a variety pattern of substituents at the β-position was mediated by a chiral diether ligand 1 to afford the corresponding β-amino esters in satisfactorily high enantioselectivities. The key to success was an addition of trimethylchlorosilane together with enoates. To the best of our knowledge, this is the first success in an external chiral ligand-controlled asymmetric conjugate addition of lithium